Over the past several years, UCSF’s Memory and Aging Center has quietly been putting itself on the map as a world leader in the study of frontotemporal dementia, or FTD, a frightening neurological disease for which there is no treatment and no cure.
In a significant next step toward a better understanding of FTD and potential treatment, Howard Rosen, MD, associate professor of neurology, has received a $10 million grant from the National Institutes of Health to embark on a five-year neuroimaging study of FTD.
The goal of the study is to quantify changes over 18 months in FTD patients, creating data that others can use to design clinical drug trials. “We hope this will make drug trials more efficient and less expensive,” Rosen said. “And it might help researchers to finish the clinical trials more quickly.”
With a disease like this, said Rosen, the advantage of imaging over, say, questionnaires or clinical observation is clear. The imaging eliminates ambiguity about changes taking place over time.The goal of the study is to quantify changes over 18 months in FTD patients, creating data that others can use to design clinical drug trials. “We hope this will make drug trials more efficient and less expensive,” Rosen said. “And it might help researchers to finish the clinical trials more quickly.”
The study will use a combination of imaging techniques – magnetic resonance imaging (MRI) combined with positron emission tomography (PET) scans. By using more than one type of imaging method, the results could be synergistic. “You might get more information by having two different kinds of images than just one,” Rosen said.
This is the first time that brain images of FTD patients will be taken over time. And UCSF – a prominent innovator in neuroimaging, thanks in part to Rosen – is well situated to do the work.
FTD is relatively rare, accounting for just 3 percent to 5 percent of all dementias. Yet in people under 60, FTD is as common as Alzheimer’s disease. And precisely because it strikes a younger population, FTD can be tricky to diagnose.
“It’s hard because physicians aren’t always looking out for degenerative diseases in middle-aged patients,” Rosen said. “It’s not the first thought that comes to your mind. You tend to think: psychiatric problems or midlife crisis.”
FTD affects certain types of language functions – what we call semantics, which reflects our knowledge about the world. “This means not just what things are called, but what they are,” said Rosen. “If you show a patient with Alzheimer’s a blender, they might not think of the word, but they know what it does. Someone with FTD wouldn’t know what it is.”
When the disease affects social and emotional functions, patients can exhibit disturbing behavioral symptoms. “People might tell dirty jokes, where they didn’t do that in the past,” said Rosen. “Or they might get very focused on very minor things, and develop weird appetites and tendencies, such as insisting on eating only red foods.”
Some patients begin to mishandle money, commit adultery or embezzle from an employer, making the disease particularly perplexing for family, friends and colleagues before a diagnosis is made.
MRI helps with diagnosis, usually showing selective atrophy of the frontal and anterior temporal lobe regions.
Rosen’s study promises to transform scientists’ understanding of the disease, particularly the changes to wiring in the brain over time.
Many patients have signed up for the neuroimaging study, and the imaging is “just starting,” said Rosen. Because it can be difficult to find enough patients for a meaningful study, UCSF has joined forces on the grant with the Mayo Clinic, another leader in FTD research, to gather 120 FTD patients. The control group will consist of 75 people. It could be three years before actual drug testing can begin.
The center mixes two of Chancellor Susan Desmond-Hellmann’s priorities for UCSF: patients and health, and discovery. Desmond-Hellmann has cited the work of Rosen and others at the Memory and Aging Center for what she calls “the intense interaction” among basic scientists, clinicians and families – all focused on and funded for specific diseases. And for the chancellor, who has spent much of her professional life developing drugs that help treat devastating illnesses, work like Rosen’s is invaluable.
Rosen pointed out that the research is particularly meaningful to patients. “Patients frequently ask me if I can look at their brain and tell them how they’re doing,” he said. “I explain to them that currently we don’t use brain images like that for diseases like FTD, but now I can tell them that new research projects will allow us to do that more in the future.”
Rosen, 45, came to UCSF in 1999 from Washington University in St. Louis, where he did a fellowship in brain imaging. He was recruited by Bruce Miller, MD, professor of neurology, who is director of the Memory and Aging Center. When Rosen arrived, he wasn’t especially interested in FTD as a research area. But inspired by Miller, he soon came to devote himself to FTD full-time.
“I recognized that this emotional side of the brain was very understudied,” he said.
Rosen came to realize how important emotional processes are to our everyday existence – even, he said, “in situations where we don’t recognize it’s playing a role.” At the same time, he recognized that there is no better example of what happens when these systems malfunction than FTD. “So, studying FTD helps us to understand more about the brain’s emotional systems, in addition to teaching us about FTD,” he said.
Photos by Elisabeth Fall